In keeping with the NCI initiative to stimulate innovative molecular epidemiologic research into the origins and progression of prostate cancer we plan to focus on the association between a new polymorphism found on the ornithine decarboxylase gene (ODC) and the development of prostate cancer. Ornithine Decarboxylase (ODC) is an enzyme in the polyamine biosynthetic pathway responsible for cellular proliferation and differentiation. Overexpression of ODC has been shown to predispose to both tumor growth and progression. We also plan to explore whether the association between the ODC genotype and the risk of prostate cancer varies by the presence of a polymorphism of the androgen receptor gene. This nested case-control study will be conducted using pre- diagnostic blood collected in 1989 as well as information on two separate questionnaires collected from men in Washington County in 1989 and 1996 as part of a large ongoing prospective study. 164 cases who have developed prostate cancer will be compared with 323 controls that are matched on age, gender and were free of other cancers at the time of diagnosis of the case. From the point of view of etiology, findings will aid in the understanding of inherited factors that influence tumor growth and progression in men with prostate cancer. From the point of view of prevention, we may be able to isolate a group of men that are at a higher risk of developing prostate cancer and possibly modify this risk by using drugs such as alpha- difluoromethylornithine (DFMO) or green tea that have been shown to inhibit ornithine decarboxylase.